The World Health Organization classification system recognizes 4 variants of JAK2 mutation–enriched myeloproliferative neoplasms (for expansion of gene symbols, use search tool at www.genenames.org): essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF), and prefibrotic PMF. All 4 disorders are characterized by stem cell–derived clonal myeloproliferation with mutually exclusive driver mutations, including JAK2, CALR, and MPL. The median survival is approximately 20 years for ET, 14 years for PV, and 6 years for PMF; age is the most important determinant of survival with the corresponding median of 33, 24, and 15 years in patients younger than 60 years. Genetic information is the second most important prognostic tool and includes karyotype, driver mutational status, and presence of specific other mutations. Karyotype has been shown to carry prognostic relevance in PV (abnormal vs normal) and PMF (unfavorable vs favorable abnormalities). Driver mutational status is prognostically most relevant in PMF; type 1/type 1-like CALR vs other driver mutational status has been associated with superior survival. In ET, arterial thrombosis risk is higher in patients with JAK2 or MPL mutations whereas MPL-mutated patients might be at risk for accelerated fibrotic progression. ASXL1 and SRSF2 mutations have been associated with inferior overall, leukemia-free, or fibrosis-free survival in both PV and PMF, and a recent targeted sequencing study has identified additional other adverse mutations in both these disorders, as well as in ET. Further enhancement of genetic risk stratification in myeloproliferative neoplasms is possible by combining cytogenetic and mutation information and developing a prognostic model that is adjusted for age.